Apomorphine (APO) and N-n-propylnorapomorphine (NPA) show definite promise as clinically useful antiparkinsonian agents. Of additional interest are recent reports that APO may be efficacious in the management of dyskinetic conditions such as Huntington's chorea and tardive dyskinesia, and in treating Gilles de la Tourette's syndrome. Paradoxical, yet real effectiveness is attributed to the use of APO in the treatment of schizophrenia and haloperidol-induced neurodysleptic syndrome. These reports should promote further interest in the basic chemistry, pharmacology, and clinical utility of apomorphine and its analogs. On the negative side, APO's poor oral activity (due to a "first-pass" effect first demonstrated in our laboratories), its short biological half-life, its toxicity (especially azotemia), and its difficult analysis in biological fluids, inhibit the widespread testing of APO in the clinic. An interdisciplinary program embracing basic chemistry and pharmacology /toxicology is necessary to study these problems and their possible interrelationships. Projected experiments include the synthesis, pharmacological evaluation, and study of the metabolic fate of APO, NPA, and their prodrugs. These investigations could lead to the design of safer, orally effective, and long acting APO-like drugs. Extended study of APO-induced azotemia in our rabbit animal model could yield metabolic correlates of a serious APO-induced side-effect in man. Throughout the proposed investigations, analytical methods will be developed for APO, NPA, their analogs and metabolites in biological fluids. Previously developed GC and HPLC procedures will be modified and improved to provide methods that are applicable to human investigations.